6-bromo-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline | 1361235-56-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-bromo-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline
• CAS: 1361235-56-4
• 化学式: C₁₆H₁₀BrFN₂O₄
• 分子量: 393.169
• InChiKey: NFIJQKPZAGITMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-bromo-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 20 % Pd(OH)2/C 、 氢气 、 三乙胺 作用下， 以 丙醇 、 乙醇 、 乙酸乙酯 为溶剂， 反应 38.0h， 生成 4-(6-ethyl-7-methoxyquinolin-4-yloxy)-3-fluorobenzenamine
  参考文献：
  名称：

  Structure-Based Design of Novel Class II c-Met Inhibitors: 2. SAR and Kinase Selectivity Profiles of the Pyrazolone Series

  摘要：

  As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with detailed SAR information, we demonstrate that the low kinase selectivity associated with class II c-Met inhibitors can be improved significantly. This work resulted in the discovery of potent c-Met inhibitors with improved selectivity profiles over VEGFR-2 and IGF-1R that could serve as useful tools to probe the relationship between kinase selectivity and in vivo efficacy in tumor xenograft models. Compound 59e (AMG 458) was ultimately advanced into preclinical safety studies.

  DOI：

  10.1021/jm201331s
• 作为产物：
  描述：

  4-溴-3-甲氧基苯胺 在 sodium hydroxide 、 三氯氧磷 作用下， 以 二苯醚 、 水 、 氯苯 为溶剂， 反应 38.74h， 生成 6-bromo-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline
  参考文献：
  名称：

  Structure-Based Design of Novel Class II c-Met Inhibitors: 2. SAR and Kinase Selectivity Profiles of the Pyrazolone Series

  摘要：

  As part of our effort toward developing an effective therapeutic agent for c-Met-dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with detailed SAR information, we demonstrate that the low kinase selectivity associated with class II c-Met inhibitors can be improved significantly. This work resulted in the discovery of potent c-Met inhibitors with improved selectivity profiles over VEGFR-2 and IGF-1R that could serve as useful tools to probe the relationship between kinase selectivity and in vivo efficacy in tumor xenograft models. Compound 59e (AMG 458) was ultimately advanced into preclinical safety studies.

  DOI：

  10.1021/jm201331s

文献信息

• OXO-PYRIDINE FUSION RING DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
  申请人：Wellmarker Bio Co., Ltd.

  公开号：EP4011885A1

  公开（公告）日：2022-06-15

  An oxo-pyridine fusion ring derivative compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof according to the present invention effectively inhibits the activity of RON and can not only effectively suppress the cell growth of cancer cell lines in which RON is activated, but also can effectively kill the cancer cell lines. Therefore, the oxo-pyridine fusion ring derivative compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof according to the present invention can be advantageously used for preventing or treating a disease associated with protein kinase activity.

  根据本发明，化学式1所代表的一种氧代吡啶融合环衍生物化合物或其药学上可接受的盐，可以有效抑制RON的活性，不仅可以有效抑制RON被激活的癌细胞系的细胞生长，还可以有效杀死癌细胞系。因此，根据本发明，化学式1所代表的氧代吡啶融合环衍生物化合物或其药学上可接受的盐可以有利地用于预防或治疗与蛋白激酶活性相关的疾病。
• [EN] OXO-PYRIDINE FUSION RING DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME<br/>[FR] DÉRIVÉ D'OXO-PYRIDINE À CYCLE CONDENSÉ ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT<br/>[KO] 옥소-피리딘 융합고리 유도체 및 이를 포함하는 약학적 조성물
  申请人：WELLMARKER BIO CO LTD

  公开号：WO2021025407A1

  公开（公告）日：2021-02-11

  본 발명에 따른 화학식 1로 표시되는 옥소-피리딘 융합고리 유도체 화합물 또는 이의 약학적으로 허용가능한 염은 RON의 활성을 효과적으로 억제하며, RON이 활성화되어 있는 암세포주의 세포 성장을 효과적으로 저해할 뿐만 아니라, 상기 암세포주를 효과적으로 사멸시킬 수 있다. 따라서, 본 발명에 따른 화학식 1로 표시되는 옥소-피리딘 융합고리 유도체 화합물 또는 이의 약학적으로 허용가능한 염은 단백질 키나제 활성과 관련된 질환의 예방 또는 치료에 유용하게 사용될 수 있다.